Relapse trigger Blocking a switch in the brain stops mice with an alcohol problem from falling off the wagon again, according to US and Israeli researchers.

The new study, published in the journal Nature Neuroscience, has identified a key brain molecule involved in the reconsolidation of alcohol-related memories triggered by the presence of alcohol. It might one day lead to a treatment for people who have alcohol abuse disorders and other addictions.

Professor Dorit Ron from the University of California, San Francisco and colleagues were interested in studying the brain mechanisms that underpin "cue-induced cravings" in people with alcoholism.

"Most patients with alcoholism will relapse within the first year of abstinence," they write. "A main cause of relapse is cue-induced drug craving, a process in which a cue that was previously associated with the reinforcing effects of alcohol elicits craving for alcohol itself."

If there was a way to erase the memory for the cue-drug association, the researchers thought, then it might be possible to reduce or prevent cue-induced relapse.

To see if this was the case, Ron and colleagues studied a group of mice that had been trained to voluntarily drink too much alcohol in specially designed cages.

After keeping the mice abstinent for ten days, the researchers then triggered alcohol cravings in some of them by returning them to the same cages and giving them just enough alcohol to taste and smell, but without any of its effects.

After this "reactivation session", the researchers measured the levels of brain protein levels in the mice that had the cravings re-ignited, and those who had not. That analysis clarified a number of things.

Pathway to memories

First, the researchers confirmed that the odour and taste of alcohol were enough to elicit reconsolidation of alcohol-associated memories. Second, they found that this process was correlated with the activation of a specific set of molecular reactions, centred on a protein complex called mTORC1.

The findings suggest that mTORC1 activation led to the expression of other proteins involved in shaping connections between brain cells.

The scientists then used a molecule called rapamycin -- currently used to prevent organ rejection after transplantation -- to block the mTORC1 signal. They found that doing this disrupted the reconsolidation of the alcohol-related memories, and prevented the mice from starting to drink alcohol again.

Interestingly, when the researchers used rapamycin on another set of mice that had been trained to drink, but had not gone through the "reactivation" process, the same effect was not seen.

"This finding indicates that rapamycin disrupts memory reconsolidation rather than the motivation to respond or consume alcohol," they suggest.

Disrupting the memory reconsolidation process by blocking mTORC1 could be an effective way of selectively interfering with alcohol-related memories while leaving non-alcohol memories intact, the researchers conclude.

"Almost every behavioural experience with alcohol includes its odour and taste," the researchers write. "Thus a reconsolidation-based strategy for relapse disruption that focuses on these cues is a promising therapeutic approach."